The Relationship between Impulsive Choice and Impulsive Action: A Cross-Species Translational Study

Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task) and impulsive action (five-choice serial reaction time task) paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT) and impulsive action (immediate and delayed memory task, IMT/DMT). Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action) and filled out the Barratt impulsiveness scale (BIS-11). Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1) self-reported impulsivity (BIS-11); (2) impulsive action (IMT/DMT and SST); (3) impulsive choice (DDT). This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology

Principal component analysis yielding 3 rotated components <i>(N = 100)</i>.

<p>Factor loadings >0.5 as significant.</p>a<p>k values were obtained by a hyperbolic decay function and log transformed.</p>b<p>IMT and DMT scores were calculated as the ratio of commission errors to correct detections.</p><p> <i>DDT: Delay Discounting Task, IMT: Immediate Memory Task, DMT: Delayed Memory Task, SSRT: Stop Signal Reaction Time, BIS-11: Barratt Impulsiveness Scale.</i></p

Correlation between impulsive choice and action after pharmacological manipulations in rats.

<p>In rats (n = 22), there was no correlation between the effects of (A) amphetamine (0.5 mg/kg, r = .22) and (B) atomoxetine (1 mg/kg, r = .21) on the two impulsivity measures: the Δ indifference point ( = drug challenge minus vehicle) of the delayed reward task and the Δ premature responses ( = drug challenge minus vehicle) in the 5-choice serial reaction time task did not correlate.</p

Correlation between impulsive choice and action in humans.

<p>In humans (n = 100), there was no correlation between impulsive choice (log DDT k value) and impulsive action measured as the ratio of commission errors to correct detections in (A) IMT (r = .11) and (B) DMT (r = .16). Within the IMT/DMT (C) there was a correlation between the ratio of commission errors to correct detections in the IMT and DMT (r = .64).</p

Pharmacological manipulation of impulsive choice and action in rats.

<p>In rats (n = 22), the preference for the large reward in the DRT decreased with increasing delays (A) and amphetamine (0.5 mg/kg) decreased impulsive choice in rats, whereas atomoxetine (1 mg/kg) increased impulsive choice. In the 5-CSRTT (B), amphetamine increased premature responding, whereas atomoxetine decreased the number of premature responses. *p<0.05, **p<0.001 compared to vehicle.</p

Correlation between impulsive choice and action in rats.

<p>In rats (n = 22), there was no correlation between impulsive action, based on premature responses in the 5-CSRTT, and impulsive choice, based on (A) the indifference point (r = −.22) or (B) the log k-value (r = .09) in the DRT. Within the 5-CSRTT (C) there was a correlation (r = .77) between impulsive action with a standard inter trial interval (ITI 5 s) and lengthened inter trial interval (ITI 7 s).</p